Is DDC p.Ala44= (c.132C>T) pathogenic?

DDC p.Ala44= (c.132C>T) is classified Likely benign in DDC (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0547%, afr); Associated with aromatic L-amino acid decarboxylase deficiency.

What condition is associated with DDC p.Ala44= (c.132C>T)?

DDC p.Ala44= (c.132C>T) is associated with aromatic L-amino acid decarboxylase deficiency (ClinVar).

How common is DDC p.Ala44= (c.132C>T) in the general population?

DDC p.Ala44= (c.132C>T) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

How is Aromatic L-amino acid decarboxylase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DDC p.Ala44=

c.132C>T · rs369201549 · VCV731874

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Conditions

aromatic L-amino acid decarboxylase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.025	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -5.3
Overall
CADD	5.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0547% African / African-American · 41/75,006 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.00533% 86/1,614,104 alleles · ultra-rare exomes 59/1,461,880 · genomes 27/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0547%	1,829
South Asian	0.0121%	8,278
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
Admixed American	0.005%	20,005
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.0022%	45,386

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DDC
Protein: p.Ala44=
Coding: c.132C>T
MANE Select: NM_001082971
dbSNP: rs369201549
Type: single nucleotide variant
Location: chr7:50543954 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.88 · 8 PDB

Full DDC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aromatic L-amino acid decarboxylase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aromatic L-amino acid decarboxylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DDC c.1041+1G>A Pathogenic/Likely pathogenic ★★ same condition
DDC c.201+1G>C Likely pathogenic ★★ same condition
DDC c.201+5G>C Pathogenic/Likely pathogenic ★★ same condition
DDC c.714+4A>T Pathogenic ★★ same condition
DDC p.Ala275Thr Pathogenic/Likely pathogenic ★★ same condition
DDC p.Ala91Val Pathogenic/Likely pathogenic ★★ same condition
DDC p.Arg160Trp Pathogenic/Likely pathogenic ★★ same condition
DDC p.Arg347Gln Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ddc-p-ala44 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown